This invention is directed to the tetradecapeptide ##STR2## pharmaceutically acceptable acid addition salts and to intermediates produced during the synthesis of the tetradecapeptide.
Somatostatin (also known as somatotropin release inhibiting factor) is a tetradecapeptide of the formula ##STR3## This tetradecapeptide was isolated from ovine hypothalamic extracts and was found to be active in inhibiting the secretion of growth hormone (GH), also known as somatotropin. In this regard, see P. Brazeau, W. Vale, R. Burgus, N. Ling, M. Butcher, J. Rivier, and R. Guillemin, Science, 179, 77 (1973).
The novel tetradecapeptide of this invention has the formula defined above and includes the non-toxic acid addition salts thereof. Its structure differs from that of somatostatin by the presence of a L-valine residue in position 10 in place of an L-threonine residue. For convenience sake, the tetradecapeptide of this invention can be referred to as L-Val.sup.10 -somatostatin.
Thus, this invention is directed to a compound selected from those of the formula ##STR4## and pharmaceutically acceptable non-toxic acid addition salts, and R-L-Ala-Gly-L-Cys(R.sub.1)-L-Lys(R.sub.2)-L-Asn-L-Phe-L-Phe-L-Trp(R.sub.5) -L-Lys(R.sub.2)-L-Val-L-Phe-L-Thr(R.sub.3)-L-Ser(R.sub.4)-L-Cys(R.sub.1)-X; in which
R is hydrogen or an .alpha.-amino protecting group; PA1 R.sub.1 is hydrogen or a thio protecting group; PA1 R.sub.2 is hydrogen or an .epsilon.-amino protecting group; PA1 R.sub.3 and R.sub.4 each are hydrogen or a hydroxy protecting group; PA1 R.sub.5 is hydrogen or formyl; and PA1 X is hydroxy or ##STR5## in which the resin is polystyrene; with the proviso that, when X is hydroxy, R, R.sub.1, R.sub.2, R.sub.3, R.sub.4, and R.sub.5 each are hydrogen, and, when X is ##STR6## R, R.sub.1, R.sub.2, R.sub.3, and R.sub.4 each are other than hydrogen.